The objective of this research is to elucidate the mechanisms involved in the physiological regulation of thyroid cell function. Principally, the studies are designed to investigate the mechanisms whereby thyrotropin induces increased thyroid hormone synthesis, cell hypertrophy and hyperplasia. In addition, the effects of excess iodide, thyroid hormones and thyrotropin itself on thyrotropin - stimulated cell function are to be studied. The experimental approach utilizes in vitro techniques employing trypsin - collagenase dispersed cells from ovine, porcine and bovine thyroid tissues, as well as thyroid tissue slices. These test systems allow the measurement of numerous aspects of thyroid cell activity, and their response to such various agents as thyrotropin, cyclic AMP, prostaglandins and the long-acting thyroid stimulator (LATS). Among those aspects of thyroid cell metabolism to be studied are cyclic AMP production, iodine metabolism, protein synthesis, and iodide transport. In addition, the research includes studies on thyroid-autoregulation designed to investigate the actions of excess iodide on thyroid cell metabolism and the response to thyrotropin stimulation. Of particular importance will be the study of the proposed iodide containing inhibitor which has been suggested to be formed within the thyroid cell following iodide pretreatment, and the mechanisms through which this substance or substances act to inhibit the iodide pump process and thyrotropin - stimulated adenylate cyclase. The effect of excess iodide on the Na-K-activated ATPase of thyroid tissue will be determined and studies performed to assess the effect of ouabain, low Na and high K on the kinetics of unidirectional iodide influx. Experiments are proposed to investigate the effects of thyrotropin and excess iodide on thyroidal blood flow. These studies will permit quantitation of both acute and chronic effects of thyrotropin on thyroid blood flow and possible actions of iodide on this parameter.